There is an enormous clinical demand for developing small caliber vascular grafts for vascular reconstructive procedures including heard or leg bypass surgery, hemodialysis access, solid organ transplantation, plastic surgery reconstruction, cancer eradicating surgery, and vascular injury repair. The long-term objective of this pre-center project is to develop a novel small diameter vascular graft with tissue engineering strategy and nanotechnology for clinical use. This project is designed to provide more experimental data supporting the central hypothesis that application of PLGA nanoparticle (NPs) delivery system and nanopatterning design of the graft surface can dramatically enhance vascular cell adhesion, differentiation and remodeling of tissue engineered small-diameter vascular grafts. This graft may maintain its mechanical property and natural compliance; reduce host immune response; provide anticoagulation surface; and accelerate vascular cell growth and remodeling, thereby maintaining a long term potency in vivo. Thus, this novel tissue-engineered vascular graft may have an excellent clinical performance equal or even better than autologous veins or arteries for vascular reconstructive procedures. This study represents a multidisciplinary approach including nanotechnology, tissue engineering, chemical engineering, cellular and molecular biology, and animal models. Success of this proposal will directly indicate the clinical applications of small diameter vascular grafts.  

Experiments are designed for achieving three specific goals: 1). To develop and optimize decellularized-heparinized porcine carotid artery graft (D-H graft) with PLGA NP-based delivery system (Dr. Chen, Baylor); 2). To optimize the laser scanning lithography (LSL) nanopatterning technology, developing techniques to alter patterning in the presence of living cells, and to utilize this unique system to study vascular endothelial cell interactions (Dr. West, Rice); and 3). To modify and optimize PLGA NPs, D-H graft, and PEG with efficient click chemistry for tissue-engineered vascular graft (Dr. Cai, UH). Synergistic interactions among investigators and experiments designed for three specific goals are carefully proposed. The project will be carried out by three major principal investigators from three different institutions with the rational of synergistic collaborations. Thus, the project is designed based on both independent investigations and synergistic interactions. Although it is a pilot project, we will establish core services or collaborations including animal core, molecular biology core, chemistry core, mechanic core, nanotechnology core and administrative core. Time frame and milestones are carefully planned. This project is very significant because it directly responds to the clinical demand for new small diameter vascular grafts, and successful results from this study should be directly translated to clinical use. Investigators have established their unique expertise and will work synergistically to use most advanced technologies. The successful results from this study should significantly advance our understanding of vascular graft design and vascular cell responses, leading to outstanding clinical performance. This study not only contributes to the Nation's knowledge of disease and disability, but also is highly relevant to military and veteran services of USA. This project will generate critical preliminary data for submitting a competitive grant such as Program Project (P01) or Specialized Center of Excellence (P50) from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) at National Institutes of Health.